title: Down-modulation of nucleoporin RanBP2/Nup358 impaired chromosomal alignment and induced mitotic catastrophe.
abstract: Chromosomal missegregation is a common feature of many human tumors. Recent studies have indicated a link between nucleoporin RanBP2/Nup358 and chromosomal segregation during mitosis; however, the molecular details have yet to be fully established. Observed through live cell imaging and flow cytometry, here we show that RNA interference-mediated knockdown of RanBP2 induced G2/M phase arrest, metaphase catastrophe and mitotic cell death. Furthermore, RanBP2 down-modulation disrupted importin/karyopherin β1 as well as the expression and localization of the Ran GTPase activating protein 1. We found that N-terminal of RanBP2 interacted with the N-terminal of importin β1. Moreover, at least a portion of RanBP2 partially localizes at the centrosome during mitosis. Notably, we also found that GTPase Ran is also involved in the regulation of RanBP2-importin β1 interaction. Overall, our results suggest that mitotic arrest and the following cell death were caused by depletion of RanBP2. Our findings point to a crucial role for RanBP2 in proper mitotic progression and faithful chromosomal segregation.
authors.affiliation: Laboratory of Molecular and Cellular Biology, Department of Biology, Faculty of Natural Systems, Institute of Science and Engineering, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Hashizume
authors.forename: A
authors.initials: A
authors.lastname: Kobayashi
authors.forename: R W
authors.initials: RW
authors.lastname: Wong
mesh_terms: D021581:Active Transport, Cell Nucleus; D000782:Aneuploidy; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism; D002877:Chromosomes, Human / Q000378:metabolism*; D015536:Down-Regulation; D016195:G2 Phase; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000737:chemistry / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D008938:Mitosis; D008954:Models, Biological; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D028884:Karyopherins; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; D034741:RNA, Small Interfering; C094493:ran-binding protein 2